Wanders R J, Van Roermund C W
Department of Clinical Biochemistry, University Hospital Amsterdam, The Netherlands.
Biochim Biophys Acta. 1993 Apr 23;1167(3):345-50. doi: 10.1016/0005-2760(93)90239-6.
We have studied the alpha-oxidation of phytanic acid in rat liver and human skin fibroblasts in order to try to resolve the controversial issue of the subcellular site of alpha-oxidation of phytanic acid. The results show that isolated mitochondria are able to alpha-oxidize phytanic acid whereas isolated peroxisomes show no phytanic acid alpha-oxidation activity. Intact hepatocytes were found to alpha-oxidize phytanic acid at a rate which is more than 20-fold higher than the activity found in postnuclear supernatant fractions incubated under optimal conditions. The alpha-oxidation of phytanic acid was found to be sensitive to inhibitors of the respiratory chain and an uncoupler of oxidative phosphorylation. Furthermore, the alpha-oxidation of phytanic acid was found to be deficient in cultured human skin fibroblasts with an inherited deficiency of cytochrome c oxidase and in fibroblasts with a deficiency of functional peroxisomes. We conclude that mitochondria are indispensable for phytanic acid alpha-oxidation. Furthermore, we propose that one (or more) of the partial reactions in phytanic acid alpha-oxidation proceeds in peroxisomes leading to the concept that phytanic acid oxidation in the intact cell requires the participation of both mitochondria and peroxisomes.
为了试图解决植烷酸α-氧化的亚细胞部位这一有争议的问题，我们研究了大鼠肝脏和人皮肤成纤维细胞中植烷酸的α-氧化。结果表明，分离的线粒体能够对植烷酸进行α-氧化，而分离的过氧化物酶体则没有植烷酸α-氧化活性。完整的肝细胞对植烷酸进行α-氧化的速率比在最佳条件下孵育的核后上清液组分中的活性高20多倍。发现植烷酸的α-氧化对呼吸链抑制剂和氧化磷酸化解偶联剂敏感。此外，在患有细胞色素c氧化酶遗传性缺陷的培养人皮肤成纤维细胞和功能性过氧化物酶体缺陷的成纤维细胞中，发现植烷酸的α-氧化存在缺陷。我们得出结论，线粒体对于植烷酸α-氧化是不可或缺的。此外，我们提出植烷酸α-氧化中的一个（或多个）部分反应在过氧化物酶体中进行，从而得出完整细胞中植烷酸氧化需要线粒体和过氧化物酶体共同参与的概念。
